Three patients with bacteremia caused by unusual gram-negative bacteria came to our attention. Two were patients with Bruton?s agammaglobulinemia patients (NIAID); the third was an HIV patient for whom the organism was referred to us for identification (VAMC). The three organisms shared features of Helicobacter-like organisms based on growth characteristics and gram stain morphology but biochemically were not compatible with described species. We initiated multiple studies to fully characterize these organisms, including rRNA gene sequencing. The organisms were extremely fastidious, microaerobic, curved, and helical bacteria that required specialized conditions to obtain satisfactory growth. Extensive biochemical studies and electron microscopy were performed to provide full descriptions of each isolate. Both patients with Brutons disease had organisms that, by rRNA gene sequencing, aligned most closely with an unusual organism, Flexispira (Helicobacter) rappini. However, DNA hybridization studies (CDC) showed that at least one of the isolates was a new taxon, distinct from F. rappini as well as from other known Helicobacter species. It is likely that the second F. rappini-like organism is similar but not identical to the first, based on a comparison of their rRNA sequences. The third organism, thought to be a Campylobacter organism by the referring hospital, did not fit known species of Campylobacter or Helicobacter. Sequencing of the rRNA gene of this organism showed it to be most closely related to a recently described Helicobacter species thus far only described from two cases in Australia. These cases help to establish that fastidious species of Helicobacter (non-H. pylori) can be significant pathogens in the immunocompromised host, causing septicemia with notable recurrences if not detected and treated appropriately. The septic-causing species are a closely related group by rRNA sequencing and cannot be accurately identified by sequencing alone. We have shown that organisms with a more than 99 percent base pair identity in the 16 S rRNA gene may show less than 70 percent homology by total genomic DNA hybridization, which is indicative of a species-level difference. The difficulty in detection and identification of these organisms is a problem for diagnostic microbiology laboratories, because special culture methods must be used to grow the organisms, and molecular methods must be used for definitive identification.